Sample container for stabilizing and aligning excised biological tissue samples for ex vivo analysis

ABSTRACT

Embodiments described herein relate to an apparatus for positioning and securing an excised biological tissue specimen for imaging and analysis. In some embodiments, an apparatus includes a sample bag defining an inner volume configured to receive a biological tissue sample, and a sealing member coupled to the sample bag. An imaging window is disposed and configured to be placed in contact with at least a portion of the biological tissue sample, and a positioning member is coupled to the imaging window and is configured to be disposed against the sealing member to substantially seal the inner volume. The positioning member includes a vacuum port disposed and configured to be aligned with a vacuum source to withdraw air from the inner volume of the sample bag.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International Patent ApplicationNo. PCT/CA2018/050874, filed Jul. 18, 2018, entitled “Sample Containerfor Stabilizing and Aligning Excised Biological Tissue Samples for ExVivo Analysis,” which claims priority to, and the benefit of, U.S.Provisional Application No. 62/533,728 filed on Jul. 18, 2017, entitled“Sample Container for Stabilizing and Aligning Excised Biological TissueSamples for Ex Vivo Analysis,” the disclosures of which are herebyincorporated by reference in their entirety.

BACKGROUND

Embodiments described herein relate to an apparatus for positioning andsecuring an excised biological tissue specimen for imaging and analysis.In clinical and surgical situations, it is often helpful to image orotherwise analyze excised biological tissue to ensure a proper tumormargin was maintained around the mass of the biological tissue. Imagingand/or otherwise analyzing excised biological tissue samples can bedifficult and time consuming, due in part to the fact that the excisedtissue is often non-uniformly shaped and the sample needs to bemaintained in the same position during analysis.

SUMMARY

Embodiments described herein relate to an apparatus for positioning andsecuring an excised biological tissue specimen for imaging and analysis.In some embodiments, an apparatus includes a sample bag defining aninner volume configured to receive a biological tissue sample, and asealing member coupled to the sample bag. An imaging window is disposedand configured to be placed in contact with at least a portion of thebiological tissue sample, and a positioning member is coupled to theimaging window and is configured to be disposed against the sealingmember to substantially seal the inner volume. The positioning memberincludes a vacuum port disposed and configured to be aligned with avacuum source to withdraw air from the inner volume of the sample bag.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a sample container, according toan embodiment.

FIG. 2 is a side-view of the sample container, according to anembodiment.

FIG. 3 is a perspective view of the sample container, according to anembodiment.

FIG. 4 is a bottom view of the sample container, according to anembodiment.

FIG. 5 shows an exploded view of a sample container, according to anembodiment.

FIG. 6 shows a cross-section of the sample container of FIG. 5.

FIGS. 7A-7E show a method for holding a biological tissue sample in asubstantially fixed position, according to an embodiment.

FIGS. 8-12 show a method for holding a biological tissue sample in asubstantially fixed position, according to an embodiment.

FIG. 13 shows a method for holding a biological tissue sample in asubstantially fixed position, according to an embodiment.

DETAILED DESCRIPTION

Embodiments described herein relate to an apparatus for positioning andsecuring an excised biological tissue specimen for imaging and/oranalysis. In some embodiments, an apparatus includes a sample bagdefining an inner volume configured to receive a biological tissuesample, and a sealing member coupled to the sample bag. An imagingwindow is disposed and configured to be placed in contact with at leasta portion of the biological tissue sample, and a positioning member iscoupled to the imaging window and is configured to be disposed againstthe sealing member to substantially seal the inner volume. Thepositioning member includes a vacuum port disposed and configured to bealigned with a vacuum source to withdraw air from the inner volume ofthe sample bag.

During certain surgical procedures, a biological sample is excised froma patient and then later analyzed to determine if the sample is diseasedand/or if any abnormalities are present in the biological tissue (e.g.,sarcoma, tumor, and/or carcinoma). The surgeon typically excisesmarginal tissue around the mass being removed to ensure that nocancerous or potentially cancerous cells are left in the patient,thereby reducing the likelihood of regrowth of the unwanted mass and/orthe spread of cancer to other parts of the body following surgery. Insome cases, the excised biological sample can be further examined usinga wide array of analytical methodologies either within the surgicaltheater, outside the surgical theater, or by an off-site third party toensure that sufficient marginal tissue was removed by the surgeon, e.g.,after a lumpectomy. For example, optical coherence tomography (OCT) canbe used to examine an excised mass of biological tissue as described inU.S. Patent Publication No. 2016/0040976 entitled, “System and Methodfor Wide Field OCT Imaging,” filed Dec. 5, 2013 (“the '976Publication”), the disclosure of which is incorporated herein byreference in its entirety. Other imaging and analysis methods can alsobe used for intrasurgical and/or extrasurgical analysis of biologicalsamples.

In the clinical and surgical situations described above where an excisedbiological sample needs to be further examined or analyzed afterexcision, it is often desirable to properly contain and position theexcised biological sample for further analysis. In other words, whenimaging and/or analyzing a biological tissue sample, the sample needs tobe placed in a fixed position or a substantially fixed position withrespect to a lens, an aperture, a discharge point, or other referencepoint of the analysis or imaging device. For example, the practitionermay have to hold the biological sample in a very precise location for anextended period in order for the analysis or imaging device tosuccessfully analyze and/or image the biological sample. Incorrectlypositioned biological samples and/or movement of the biological samplesduring imaging/analysis can lead to lower quality images/results and cancompromise the quality of patient care.

It should also be noted that the terms “coupled” or “coupling” as usedherein can have several different meanings depending on the context inwhich these terms are used. For example, the terms coupled or couplingcan have a mechanical, electrical or optical connotation. For example,depending on the context, the terms coupled or coupling may indicatethat two elements or devices can be physically, electrically oroptically connected to one another or connected to one another throughone or more intermediate elements or devices via a physical, electricalor optical element such as, but not limited to a wire, fiber optic cableor waveguide, for example.

As used herein, the term “about” and “approximately” generally mean plusor minus 10% of the value stated, for example about 250 μm would include225 μm to 275 μm, approximately 1,000 μm would include 900 μm to 1,100μm.

In the following passages, different aspects of the embodiments aredefined in more detail. Each aspect so defined may be combined with anyother aspect or aspects unless clearly indicated to the contrary. Inparticular, any feature indicated as being preferred or advantageous maybe combined with at least one other feature or features indicated asbeing preferred or advantageous.

Described herein are various example embodiments of systems,apparatuses, and methods that can be used to accurately and preciselyposition an excised biological tissue sample relative to an imagingdevice during imaging and/or during a storage period. The systems,apparatuses, and methods described herein have various applications suchas, but not limited to medical applications, inter- or intra-surgicalanalysis, veterinary applications, laboratory applications, and ex vivoanalysis of excised tumors, growths, nodules, melanoma, appendages,organs, and other excised biological materials. A typical tissue samplehas a surface area of approximately 200 cm² and the surface of thetissue sample may be irregular, leading to complications during imagingor analysis of the excised biological tissues. Excised tissue samplescan also be difficult to handle without introducing contaminants and/orcausing damage to the tissue sample during handling of the sample andprior to imaging or analysis. In order to reduce the difficulty ofsample handling, increase the ease and repeatability of positioning andmaintaining the position of samples during imaging or analysis, andreduce the likelihood of introducing contaminants to the tissue sample,systems, apparatuses, and methods described herein can be used.

In some embodiments, an apparatus for holding a biological tissue samplein a fixed position or a substantially fixed position during imaging caninclude a sample bag defining an inner volume and configured to hold thebiological tissue during imaging. In some embodiments, the sample bagcan have an opening and define a cavity therewithin. In someembodiments, the sample bag can be configured to receive the biologicaltissue sample and have a first volume in a first configuration and asecond volume less than the first volume in a second configuration.

In some embodiments, the apparatus can include a sealing member coupledto the sample bag and configured to maintain the sample bag in anairtight condition. In some embodiments, the sealing member can becoupled to a circumference of the opening of the sample bag.

In some embodiments, the apparatus can include an imaging windowdisposed and configured to be placed in contact with at least a portionof the biological tissue sample. In other words, the biological tissuesample can be positioned within the sample bag and can rest upon theimaging window during use of the apparatus. In some embodiments, theimaging window can fit within the opening of the sample bag and/or anaperture of the sealing member. In some embodiments, the imaging windowcan be disposed within the opening of the sample bag, and a positioningmember coupled to the imaging window and configured to be disposedagainst the sealing member. In some embodiments, the imaging window canbe configured to be in contact with a portion of the biological tissuesample.

In some embodiments, the apparatus can include a positioning membercoupled to the imaging window and configured to be disposed against thesealing member. In some embodiments, the positioning member can includea vacuum port or a plurality of vacuum ports disposed and configured tobe aligned with a vacuum source to withdraw air from the inner volume ofthe sample bag. In some embodiments, the inner volume of the sample bagcan be substantially sealed when the positioning member is disposedagainst the sealing member. In some embodiments, the vacuum source is avacuum pump. In some embodiments, the vacuum port can be sealed suchthat a partial vacuum can be maintained within the apparatus once thevacuum source is disconnected. In some embodiments, the positioningmember can include a first portion and a second portion, the sealingmember disposed between the first portion and the second portion suchthat the inner volume is substantially sealed. In some embodiments,withdrawing air from the cavity of the sample bag moves the sample bagfrom the first configuration to the second configuration.

In some embodiments, the apparatus can include a locking mechanismconfigured to maintain the sealing member in contact with thepositioning member. In some embodiments, the locking mechanism caninclude a channel, e.g., a channel having a first end that issubstantially open and a second end that is substantially closed. Insome embodiments, the apparatus can include an alignment elementconnected to the positioning member, a first alignment markingindicating the first end of the channel, and a second alignment markingindicating the second end of the channel. In some embodiments, thealignment element is configured to move between the first alignmentmarking and the second alignment marking as the positioning member isrotationally connected to an imaging device, a base, and/or a receivingmember. In some embodiments, alignment between the alignment element andthe second alignment marking indicates proper alignment of the vacuumport with the vacuum system or the plurality of vacuum ports with thevacuum system. In some embodiments, the vacuum system can include acorresponding vacuum port or plurality of vacuum ports disposed withinthe imaging device, the base, and/or the receiving member. In someembodiments, the locking mechanism can include a ridge protruding from asurface of the locking mechanism, the ridge dimensioned and configuredto be lockably disposed within a channel defined within the imagingdevice, the base, and/or the receiving member.

In some embodiments, at least one of the sample bag, the sealing member,the imaging window, and the positioning member is reusable. In someembodiments, at least one of the sample bag, the sealing member, theimaging window, and the positioning member can be sterilized in anautoclave before reuse.

In some embodiments, the apparatus can include an electronic sensorconfigured to close a circuit when the vacuum port is properly alignedwith the vacuum system and an indicator light connected to the circuitand configured to illuminate when the circuit is closed. In someembodiments, the apparatus can also or alternatively include an audiblealarm connected to the circuit and configured to produce a sound whenthe circuit is closed.

In some embodiments, the apparatus can include the receiving member, thereceiving member including or defining a channel to which a portion ofthe positioning member is configured to be disposed. In someembodiments, the portion of the positioning member can include a ridgeor other element configured to fit snugly within the channel. In someembodiments, the ridge or other element of the positioning member can beor substantially be the same shape as the inner cavity of the channeldefined by one or more walls of the channel. In some embodiments, theapparatus can include a plurality of registration points disposed aboutthe receiving member and configured to arrest movement of thepositioning member once the portion of the positioning member isdisposed within the channel. In some embodiments, the registrationpoints can include a tab, a tag, a stub, a protuberance, a bump, aroughened portion, or any other suitable feature disposed on or definedby the positioning member, locking mechanism, and/or the receivingmember, the base, or the imaging device. In some embodiments, theregistration points can disallow rotational movement of the positioningmember and/or the locking mechanism with respect to the receivingmember, the base, or the imaging device. In some embodiments, theregistration points can be visual aids such that a user can discontinuerotational movement of the positioning member and/or the lockingmechanism with respect to the receiving member, the base, or the imagingdevice once the registration point is aligned with a correspondingalignment marking or other feature. In some embodiments, the receivingmember can be configured to be coupled to the imaging device or can be apart of the imaging device such that the biological tissue sample issecurely positioned against the sample window and readily available foranalysis. In some embodiments, analysis can include the communication ofelectromagnetic energy from the imaging device, through the samplewindow, to the biological tissue sample.

The present disclosure also describes methods for making and using anapparatus configured to accurately position the excised biologicalsample relative to the imaging device and for maintaining accuratepositioning for a period of time. In some embodiments a method forholding a biological tissue sample in a substantially fixed positionduring imaging can include receiving the biological tissue sample intothe inner volume of the sample bag, the sample bag coupled to thesealing member. In some embodiments, the method can also includedisposing the imaging window into contact with a portion of thebiological tissue sample. In some embodiments, the imaging window can bedisposed within or against a surface of the positioning member and/orthe locking mechanism. In some embodiments, the method can includecoupling the positioning member to the imaging window to form a samplecontainer such that the biological tissue sample is substantially sealedwithin the sample container. In other words, after disposing the excisedbiological tissue sample into the sample bag, the sample bag can bedisposed though an opening or orifice of the positioning member orlocking mechanism with the imaging window disposed therebetween. In someembodiments, when the biological tissue sample is disposed within thesample bag and sealed therewithin using the imaging window held in placeby the positioning member and/or the locking mechanism, the samplecontainer is thereby formed. In some embodiments, the method can furtherinclude removably locking the sample container to a receiving member,the receiving member being configured to hold the sample container inplace with regard to the imaging device. In some embodiments, the methodcan further include withdrawing air from the inner volume of the samplebag. In some embodiments, withdrawing air from the inner volume of thesample bag can cause the sample bag to move from the first configurationto the second configuration. In some embodiments, in the secondconfiguration, the sample bag is drawn substantially tightly about thebiological tissue sample and holds the biological tissue sample in placeagainst the imaging window. In some embodiments, disposing the imagewindow into contact with the portion of the biological tissue sample toform the sample container can include rotatably locking the imagingwindow to a sealing member.

In some embodiments, a method for making the sample holder configured tohold a biological tissue sample in a substantially fixed position duringimaging can include coupling a sample bag to an imaging window. In someembodiments, when the imaging window is coupled to the sample bag, theinner volume of the sample bag can be substantially airtight. In someembodiments, the method can include coupling the sample bag to a lockingmechanism by disposing the sample bag through an aperture of the lockingmechanism such that the imaging window is disposed against a surface ofthe locking mechanism. In some embodiments, the locking mechanism candefine a channel and can include a first plurality of vacuum ports. Insome embodiments, the channel can include a first end that is open and asecond end that is closed. In some embodiments, the method can furtherinclude rotatably coupling the locking mechanism to a receiving member.In some embodiments, the receiving member can include a ridge configuredto be slidably disposed within the channel and a second plurality ofvacuum ports. In some embodiments, the second plurality of vacuum portscan be configured to be substantially aligned with the first pluralityof ports when the locking mechanism is rotatably coupled to thereceiving member.

FIG. 1 shows a schematic illustration of a sample container 100 (alsoreferred to herein as “specimen container” or “sample holder”) thatincludes a sample bag 110 defining an inner volume configured to receivethe biological tissue sample (not shown), and a sealing member 120coupled to the sample bag 110. In some embodiments, an imaging window130 is disposed and configured to be placed in contact with at least aportion of the biological sample. In some embodiments, a positioningmember 140 is coupled to the imaging window 130 and is configured to bedisposed against the sealing member 120 to substantially seal the innervolume of the sample bag 110. In some embodiments, the positioningmember 140 can include at least one vacuum port 150 disposed andconfigured to be aligned with a vacuum source to withdraw air from theinner volume of the sample bag 110. In some embodiments, the samplecontainer 100 further includes a locking mechanism 160 configured toselectively engaged with at least one of the positioning member 140and/or the sealing member 120.

In some embodiments, the sample bag 110 is dimensioned and configured tohold or contain the biological tissue sample) during analysis and/or fora period of time after analysis has been conducted. In some embodiments,the sample bag 110 is dimensioned and configured to hold or contain thebiological tissue sample for an extended period of time, during whichtime the sample is stored and/or transported for additional analysisand/or imaging. In some embodiments, the sample bag 110 is dimensionedand configured to be in a first configuration in which the inner volumeof the sample bag 110 is at or is substantially at a maximum. In someembodiments, the biological tissue sample can be disposed within thesample bag 110 when the sample bag 110 is in the first configuration. Insome embodiments, withdrawing air from the sample bag 110 can transitionthe sample bag 110 from the first configuration to a secondconfiguration in which the inner volume of the sample bag 110 is lowerthan in the first configuration. In some embodiments, once a portion ofair is withdrawn from the sample bag 110, the inner volume of the samplebag 110 can be substantially similar to the volume of the biologicaltissue sample. In some embodiments, the portion of air removed from thesample bag 110 can create a partial vacuum within the sample bag 110. Insome embodiments, when the sample bag 110 is in the secondconfiguration, the sample bag 110 can hold the biological tissue samplein place against the imaging window 130.

In some embodiments, the sample holder 100 and any subcomponents thereofcan be sterilized such that a contacting surface (inner surface) of thesample container 100 is substantially free of biological contaminants,bacteriological contaminants, viral contaminants, chemical contaminants,or other contaminants. In some embodiments, “substantially free ofcontaminants” refers to any amount of contaminant present at or belowthe detectable limit using currently available analytical methods andaccording to current good manufacturing practice (cGMP). In someembodiments, the sample container 100 can be sterilized chemically,thermally, using a liquid solvent, via bombardment of electromagneticenergy, via irradiation from a radiological source, vi any othersuitable methods, or any combination thereof. In some embodiments, thesample container 100 (or portions thereof) can be autoclaved prior touse.

In some embodiments, the sample bag 110 can be made from any suitablyflexible, deformable, and/or elastic material disclosed herein. In someembodiments, the sample bag 110 can be substantially transparent inorder to allow the practitioner to view the sample contained within. Insome embodiments, the sample bag 110 can be highly flexible, allowing avacuum system, a practitioner, any other cause, or any combinationthereof to draw the bag more closely around the sample. In someembodiments, the sample bag 110 can include a polymer, a rubber, avinyl, a ethyl compound, an imide, polyvinyl chloride, polypropylene,polyethylene, polystyrene, nylon, polyethylene terephthalate, polyimide,polycarbonate, acrylonitrile butadiene, polyetheretherketone,polyurethane, and any admixtures thereof

In some embodiments, the sample bag 110 can be sufficiently robust(e.g., thick and/or durable) to withstand vacuum being drawn on thesubstantially sealed sample container 100 without being damaged and/orwithout compromising the airtight seal. In some embodiments, a thicknessof the sample bag 110 can be between about 10 μm and about 5 mm, betweenabout 15 μm and about 4.5 mm, between about 30 μm and about 4 mm,between about 75 μm and about 3 mm, between about 100 μm and about 3 mm,between about 150 μm and about 2.5 mm, between about 200 μm and about 2mm, between about 300 μm and about 2 mm, between about 500 μm and about1.5 mm, and between about 750 μm and about 1 mm, inclusive of all rangesand values therebetween. In some embodiments, the thickness of thesample bag 110 can be greater than about 10 μm, greater than about 50μm, greater than about 100 μm, greater than about 150 μm, greater thanabout 200 μm, greater than about 250 μm, greater than about 300 μm,greater than about 350 μm, greater than about 500 μm, greater than about750 μm, greater than about 1 mm, greater than about 2 mm, greater thanabout 3 mm, greater than about 4 mm, or greater than about 5 mm,inclusive of all ranges and values therebetween. In some embodiments,the thickness of the sample bag 110 can be less than about 5 mm, about4.5 mm, about 4 mm, about 3.5 mm, about 3 mm, about 2.5 mm, about 2 mm,about 1.5 mm, about 1 mm about 750 μm, about 500 μm, about 250 μm, about150 μm, about 100 μm, about 50 μm, or about 10 μm, inclusive of allvalues and ranges therebetween.

In some embodiments, the sample bag 110 can be coupled to the sealingmember 120. In some embodiments, the sample bag 110 can be coupled tothe sealing member 120 by interposing a portion of the sample bag 110between two or more portions (e.g., layers) of the sealing member 120.For example, the two portions or more of the sealing member 120 can becoupled mechanically, with an adhesive, thermally bonded, or anycombination thereof. In some embodiments, the sample bag 110 can becoupled to the sealing member with an adhesive. In some embodiments, thesample bag 110 can be coupled to the sealing member 120 through athermal fusing process. In some embodiments, the sample bag 110 can becoupled to the sealing member 120 through a thermochemical melding ofthe two materials. In some embodiments, the sample bag 110 can be formedfrom the sealing member 120. In some embodiments, the sample bag 110 canbe formed by extruding the sealing member 120 with no center hole andthen forming the sample bag 110 from the sealing member 120 throughthermal and/or physical deformation (e.g., stretching) of a portion ofthe sealing member 120. In some embodiments, deformation of a portion ofthe sealing member 120 (e.g., in the center) can define an aperture ofthe sealing member 120 and the opening of the sample bag 110. In someembodiments, the deformed portion of the sealing member 120 can bedeformed to form the sample bag 110 therefrom. In some embodiments, theportion (e.g., center) of the sealing member 120 can be deformed to theextent that the material becomes sufficiently elastic and/or deformableand such that the formed sample bag 110 can transition from the firstconfiguration to the second configuration when air is withdrawn from thesample bag 110.

In some embodiments, the sample bag 110 maintains a first configurationwhen no vacuum is drawn against the sample container 100. In someembodiments, the sample bag 110 can be substantially extended to itsmost voluminous state in the first configuration. In other words, theinner volume of the sample bag 110 is at or near a maximum volume in thefirst configuration. In some embodiments, once vacuum is drawn on thesample container 100 by withdrawing air from the sample bag 110, thesample bag 110 can transition from the first configuration to a secondconfiguration. In some embodiments, the inner volume of the sample bag110 in the second configuration is less than the inner volume of thesample bag 110 in the first configuration. In some embodiments, theinner volume of the sample bag 110 in the second configuration can besubstantially similar to the volume of the biological tissue sample.Said another way, once vacuum is drawn on the sample container 100substantially all of the air is removed from the inner volume of thesample bag 110 such that the biological tissue sample occupies nearly100% of the inner volume. In some embodiments, the sample bag 110 cantransition to a third configuration once the vacuum system isdisconnected from the sample container 100 or the partial vacuum isotherwise relieved. In some embodiments, the sample bag 110 cantransition to the third configuration while the vacuum system is stillconnected and the sample container 100 remains under partial vacuum. Insome embodiments, the inner volume of the sample bag 110 in the thirdconfiguration can be less than the inner volume of the sample bag 110 inthe first configuration but greater than the inner volume of the samplebag 110 in the second configuration. In some embodiments, the sample bag110 can move from the second configuration back to substantially thefirst configuration once the sample container 100 is disconnected fromthe vacuum system or air is otherwise communicated back into the samplebag 110. In some embodiments, the sample bag 110 can remainsubstantially in the second configuration once the sample container 100is disconnected from the vacuum system or air is otherwise communicatedback into the sample bag 110. In some embodiments, the sample bag 110can remain substantially in the second configuration because the vacuumport 150 can be sealed closed such that air is not allowed to becommunicated back in to the sample bag 110. In some embodiments, sealingthe vacuum port 150 can allow for the movement of the sample container100 between different imaging devices and/or can allow the biologicaltissue sample to be stored in the sample container 100 without becomingcontaminated.

The sealing member 120 can be a gasket, the gasket coupled to the samplebag 110 such that a seal is formed between the sample bag 110 and thesealing member 120. In some embodiments, the sealing member 120 can bedisposed against a surface to form a seal. In some embodiments, thesealing member 120 can be disposed between two surfaces in order tosubstantially seal the sample container 100. In some embodiments, thesealing member 120 can define a center hole (not shown). In someembodiments, the sealing member 120 can be placed into abutment with asurface of the positioning member 140 during use of the sample container100. In some embodiments, the abutment of the sealing member 120 againstthe surface of the positioning member 140 creates a seal or partial sealbetween the inner volume of the sample bag 110 and the outsideenvironment. In some embodiments, the positioning member 140 isconnected to the sealing member 120 to form a releasable seal between asurface of the sealing member 120 and the surface of the positioningmember 140. In some embodiments, the positioning member 140 isinterposed between the sealing member 120 and the imaging device oraperture defined therein. In some embodiments, the sealing member 120 isinterposed between the positioning member 140 and the imaging device oraperture defined therein. In some embodiments, the sealing member 120substantially covers a top portion or top side of the positioning member140.

In some embodiments, the sealing member 120 can be made from anysuitably material, including but not limited to plastics, rubbers,synthetic rubbers, neoprene, polyethylene, polyethylene terephthalate,polytetrafluoroethylene, nitrile, silicone, fiberglass,polychlorotrifluoroethylene, buna rubber, viton, fluoropolymer, teflon,polyesters, high-density polyethylene, low-density polyethylene,ultrahigh-density polyethyelen, polyvinyl chloride, polyvinylidenechloride, polypropylene, polystyrene, high impact polystyrene,polyamides, acrylonitrile butadiene styrene, polycarbonate,polyethyelen-acrylonitrile butadienet styrene,polycarbonate-acrylonitrile butadiene styrene, polyurethanes, maleimide,bismaleimide, melamine formaldehyde, phenolics, plastarch, polyepoxide,polyetheretherketone, polyetherimide, polyimide, polylactic acid,polymethyl methacrylate, polytetrafluoroethylene, urea-formaldehyde,furan, polysulfone, nylon, and admixtures thereof. In some embodiments,the sealing member 120 can include a single layer of any of thedisclosed materials. In some embodiments, the sealing member 120 caninclude a plurality of layers joined together. In some embodiments, thesealing member can include two to eight layers of material, inclusive ofall values and ranges therebetween. In some embodiments, each of theplurality of layers can have substantially the same dimensions and canbe formed from the same material or mixture of materials. In someembodiments, at least one of the plurality of layers has a differentdimension than at least one other layer. In some embodiments, at leastone of the plurality of layers is made from a different material ormixture of materials than at least one other layer.

In some embodiments, the sealing member 120 can have a dimensionalthickness measured in the direction perpendicular to the surfaceconfigured to contact the positioning member 140. In some embodiments,the sealing member 120 can have a thickness sufficient to provide asubstantially airtight seal when positive pressure is applied againstthe sealing member 120. In some embodiments, the sealing member 120 canhave a thickness sufficient to provide a substantially airtight sealwhen a vacuum is drawn against the sealing member 120. In someembodiments, the sealing member 120 can have a thickness between about10 μm and about 25 mm, between about 250 μm and about 15 mm, betweenabout 500 μm and about 10 mm, between about 750 μm and about 9 mm,between about 850 μm and about 8 mm, between about 1 mm and about 7 mm,between about 1 mm and about 6 mm, between about 1.5 mm and about 5 mm,and between about 2 mm and about 4 mm, inclusive of all ranges andvalues therebetween. In some embodiments, the sealing member 120 canhave a thickness greater than about 10 μm, greater than about 50 μm,greater than about 100 μm, greater than about 250 μm, greater than about500 μm, greater than about 750 μm, greater than about 1 mm, greater thanabout 3 mm, greater than about 5 mm, greater than about 7 mm, greaterthan about 9 mm, or greater than about 11 mm, inclusive of all rangesand values therebetween.

The imaging window 130 at least partially defines the inner volume ofthe sample container 100 along with the sample bag 110, and isconfigured to be placed against an imaging device such that the imagingdevice can take images of the biological sample through the imagingwindow 130. In some embodiments, the imaging window 130 can beconfigured to be placed in contact with at least a portion of thebiological tissue sample. In some embodiments, the imaging window 130can be dimensioned and configured to be planar. In some embodiments, theimaging window 130 can be dimensioned and configured to be concave,providing a depression or other such concavity that at least partiallyholds the biological tissue sample in place during analysis and/orimaging. In some embodiments, the imaging window 130 can be fixedlycoupled to the positioning member 140. In some embodiments, the imagingwindow 130 can be removably coupled to the positioning member 140. Insome embodiments, the imaging window 130 can be disposed within anaperture (not shown) defined by the positioning member 140. In someembodiments, the imaging window 130 can be formed from the same materialand/or at the same time as the positioning member 140. In other words,the imaging window 130 can be non-delineable element of the positioningmember 140 (i.e., integrally formed with the positioning member 140).

In some embodiments, the imaging window 130 can have a thicknesssufficient to withstand any vacuum pressure disclosed herein. In someembodiments, the imaging window 130 can be thin enough so as to allowlight particles, electromagnetic energy, or other energy forms to passthrough the imaging window 130. In some embodiments, the thickness ofthe imaging window 130 can be between about 10 μm and about 15 mm,between about 250 μm and about 13 mm, between about 500 μm and about 10mm, between about 750 μm and about 9 mm, between about 850 μm and about8 mm, between about 1 mm and about 7 mm, between about 1 mm and about 6mm, between about 1.5 mm and about 5 mm, and between about 2 mm andabout 4 mm, inclusive of all ranges and values therebetween. In someembodiments, the thickness of the imaging window 130 can be greater thanabout 10 μm, greater than about 50 μm, greater than about 100 μm,greater than about 250 μm, greater than about 500 μm, greater than about750 μm, greater than about 1 mm, greater than about 3 mm, greater thanabout 5 mm, greater than about 7 mm, greater than about 9 mm, greaterthan about 11 mm, greater than about 13 mm, or greater than about 15 mm,inclusive of all ranges and values therebetween.

In some embodiments, the imaging window 130 can be made from anysuitably rigid, suitably strong, and suitably transparent material. Insome embodiments, the imaging window 130 can be made of glass,borosilicate glass (e.g., Schott BK7 or H-K9L from CDGM Glass CompanyLtd.), amorphous polyolefins, cyclo olefin polymers, cellulose acetate,high-density polyethylene, low-density polyethylene, high-impactpolystyrene, polyetheretherketone, polyesters, polyvinyl chloride,polyvinylidene chloride, polypropylene, polyamides, acrylonitrilebutadiene styrene, polyurethanes, poly(methyl methacrylate),polycarbonate, polyethylene, polyethylene terephthalate, polylacticacid, polyvinyl butyral, pyrex, nitrocellulose, acrylates, any othermaterial disclosed herein, and any other material suitably transparentand durable to enable imaging/analysis while also withstanding partialvacuum conditions, and combinations or admixtures thereof.

As described herein, the positioning member 140 can be coupled to and/orintegrally formed with the imaging window 130. In some embodiments, thepositioning member 140 can be non-uniformly shaped and the sealingmember 120 can be dimensioned and configured such that the abutment ofthe sealing member 120 against the positioning member 140 can result inthe sample container 100 being substantially sealed.

In some embodiments, the shape of the positioning member 140 can be inthe form of a torus, hemisphere, disk, hoop, ring, halo, circle, planarcircle, cuboid, ellipsoid, sphere, cylinder, hexagonal prism, pentagonalprism, rhombus, frustum, irregular polygon, any other suitable shape, orcombinations thereof In some embodiments, the positioning member 140defines the aperture approximately in the center of the positioningmember 140, and the imaging window 130 is disposed within the aperturedefined by the positioning member 140. In some embodiments, the imagingwindow 130 is coupled to the positioning member 140 such that asubstantially airtight seal is formed. In some embodiments, thepositioning member 140, the imaging window 130, the sealing member 120,and the sample bag 110 collectively define the inner volume in which thebiological sample is disposed.

In some embodiments, the positioning member 140 can be dimensioned andconfigured to abut a portion of an imaging device. In some embodiments,the positioning member 140 can be configured to position the sample ofbiological tissue in three-dimensional space relative to a lens or probeof the imaging device. In some embodiments, the positioning member 140can be disposed at least partially within a recess of the imagingdevice. In some embodiments, the positioning member 140 can include analignment feature to help ensure the sample container 100 is properlypositioned with respect to the imaging device. For example, in someembodiments, the positioning member 140 can include alignment markings,fiducial marks, protuberances, keys, mechanical stops, recesses and/orthe like that are designed to mate with the imaging device so that thesample container 100 is properly positioned with respect to the imagingdevice. Similarly, the imaging device can include alignment markings,fiducial marks, protuberances, keys, mechanical stops, recesses and/orthe like that are designed to mate with the sample container 100. Inother words, either the sample container 100, the imaging device, orboth can include alignment features to help ensure the sample container100 is properly positioned with respect to the imaging device.

In some embodiments, the positioning member 140 can have an outersurface and an inner surface. In some embodiments, the inner surface ofthe positioning member 140 can define a groove or a plurality ofgrooves. In some embodiments, the groove can be substantially filledwith a plurality of indents. In some embodiments, the inner surface ofthe positioning member 140 can include threads. In some embodiments, thethreads on the inner surface of the positioning member 140 can bedimensioned and configured to engage receiving threads within anaperture of the imaging device.

In some embodiments, the positioning member 140 can further include aplurality of tabs on the outer surface. In some embodiments, theplurality of tabs is between two and six tabs, inclusive of all rangesand values therebetween.

In some embodiments, the positioning member 140 can be made of anysuitable material, including but not limited to polyesters, polyethyleneterephthalate, polyethylene, high-density polyethylene, polyvinylchloride, polyvinylidene chloride, low-density polyethylene,polypropylene, polycarbonate, polystyrene, high impact polystyrene,poyamides, acrylonitrile butadiene styrene, polyethylene-acrylonitrilebutadiene styrene, polycarbonate—Acrylonitrile butadiene styrene,polyurethanes, maleimide, bismaleimide, melamine formaldehyde,plastarch, phenolics, phenol formaldehydes, polyepoxide,polyetheretherketone, polyetherimide, polyimide, polylactic acid,polymethyl methacrylate, polytetrafluoroethylene, urea-formaldehyde,furan, silicone, polysulfone, natural rubber, synthetic rubber, carbonfiber, nylon, cotton, wood, aluminum, bismuth, chromium, cobalt, copper,gallium, gold, indium, iron, lead, magnesium, mercury, nickel, rhodium,scandium, silver, titanium, tin, zinc, steel, stainless steel, brass,bronze, and admixtures thereof

In some embodiments, the diameter of the positioning member 140 isbetween about 1 cm and about 35 cm. In some embodiments, the diameter ofthe positioning member 140 is greater than about 1 cm, greater thanabout 3 cm, greater than about 5 cm, greater than about 10 cm, greaterthan about 15 cm, greater than about 20 cm, greater than about 25 cm,greater than about 30 cm, inclusive of all values or rangestherebetween. In some embodiments, the diameter of the positioningmember 140 is between about 1 cm and about 30 cm, between about 2 cm andabout 30 cm, between about 3 cm and about 25 cm, between about 4 cm andabout 20 cm, between about 5 cm and about 15 cm, between about 6 cm andabout 14 cm, between about 7 cm and about 13 cm, between about 8 cm andabout 12 cm, between about 9 cm and about 11 cm, inclusive of all valuesand ranges therebetween. In some embodiments, the diameter of thepositioning member 140 is less than about 3 cm, less than about lessthan about 5 cm, less than about 7 cm, less than about 9 cm, less thanabout 11 cm, less than about 13 cm, less than about 15 cm, less thanabout 17 cm, less than about 19 cm, less than about 21 cm, less thanabout 23 cm, less than about 25 cm, less than about 29 cm, less thanabout 31 cm, less than about 33 cm, less than about 35 cm, inclusive ofall values and ranges therebetween.

The vacuum port 150 is dimensioned and configured to be aligned with(i.e., placed in fluid communication) a vacuum source (not shown), suchthat the vacuum source can draw at least a partial vacuum on the samplecontainer 100. Said another way, when the vacuum port 150 is alignedwith the vacuum source, air can be drawn out of the sample bag 110 viathe vacuum port. In some embodiments, the vacuum source can be a part ofthe imaging device. In some embodiments, the vacuum port 150 can be usedto releasably couple the sample container 100 to the imaging device viathe vacuum system as the vacuum system draws a partial vacuum on thesample container 100 such that the sample bag 110 is drawn around thebiological tissue sample to hold it in place against the imaging window130 during imaging/analysis.

In some embodiments, the vacuum port 150 can be disposed within thepositioning member 140. In some embodiments, the vacuum port 150 can bea single vacuum port. In some embodiments, the vacuum port 150 can be aplurality of vacuum ports. In some embodiments, the plurality of vacuumports 150 can be between two and ten, between two and eight, between twoand six, between two and five, between two and four, between two andthree, greater than two, greater than four, greater than six, greaterthan eight, or greater than 10, inclusive of all ranges and valuetherebetween.

In some embodiments, the amount of vacuum drawn, as absolute pressure inatmospheres (atm), on the substantially airtight sample container 100can be from about 0.01 atm to about 0.97 atm, from about 0.1 atm toabout 0.95 atm, from about 0.15 atm to about 0.9 atm, from about 0.2 atmto about 0.85 atm, from about 0.25 atm to about 0.8 atm, from about 0.3atm to about 0.75 atm, from about 0.35 atm to about 0.7 atm, from about0.4 atm to about 0.65 atm, from about 0.45 atm to about 0.6 atm, andfrom about 0.5 atm to about 0.8 atm, inclusive of all values and rangestherebetween. In some embodiments, the amount of vacuum drawn asabsolute pressure on the substantially airtight sample container 100 canbe less than about 0.97 atm, less than about 0.95 atm, less than about0.9 atm, less than about 0.8 atm, less than about 0.7 atm, less thanabout 0.6 atm, less than about 0.5 atm, less than about 0.4 atm, lessthan about 0.3 atm, less than about 0.2 atm, and less than about 0.1atm, inclusive of all values and ranges therebetween.

In some embodiments, the plurality of vacuum ports 150 disposed withinor adjacent to the positioning member 140 are evenly disposedcircumferentially about the positioning member 140. In some embodiments,the evenly disposed vacuum ports 150 can at least partially cause thesample bag 110 to be drawn about the biological tissue sample moreevenly and to hold the biological tissue sample in a more substantiallyfixed position against the imaging window 130.

In some embodiments, the vacuum port 150 can further include a valve(not shown). In some embodiments, the valve can be actuated closed inorder to maintain a state of partial vacuum within the sample container100. In some embodiments, the state of partial vacuum within the samplecontainer 100 can be maintained for a period of time. In someembodiments, the state of partial vacuum within the sample container 100can be maintained for a period of time in order to fix the biologicaltissue sample against the imaging window 130 during storage, transport,and/or additional analysis of the biological tissue sample without theneed for a vacuum system to continuously maintain the vacuum conditionswithin the sample container 100 over the same period of time.

In some embodiments, drawing vacuum on the sample container 100 resultsin the sample bag 110 being drawn tightly around the biological tissuesample, holding the biological tissue sample substantially immovably onthe imaging window 130. In some embodiments, the biological tissuesample is held substantially immovably in a particular position by boththe positioning member 140 being releasably locked with respect to theimaging device (i.e., within an aperture) using the locking mechanism160, and the air within the inner volume of the sample bag 110 beingsubstantially evacuated from the inner volume.

In some embodiments, the locking mechanism 160 can be coupled to atleast one of the positioning member 140 and/or the sealing member 120.In some embodiments, the locking mechanism 160 can be coupled to boththe positioning member 140 and the sealing member 120. In someembodiments, the locking mechanism 160 can be coupled to both thepositioning member 140 and the imaging device. In some embodiments, thelocking mechanism 160 is configured to lock the positioning member 140against the imaging device. In some embodiments, the locking mechanism160 is configured to lock the positioning member 140 in an aperture ofthe imaging device. In some embodiments, the locking mechanism 160 isdisposed between the two portions of the positioning member 140 suchthat the two portions of the positioning member 140 can be lockedtogether. In some embodiments, the locking mechanism 160 is disposedbetween the two portions of the positioning member 140, such that thesealing member 120 can be interposed between the two portions of thepositioning member. In some embodiments, the locking mechanism 160 canbe configured such that the positioning member 140 can be immovablyconnected to at least a portion of the sealing member 120.

In some embodiments, the locking mechanism 160 can be a first threadedelement dimensioned and configured to rotationally engage with a secondthreaded element. In some embodiments, the first and/or second threadedelement can include stops or extents. In some embodiments, the stops orextents can be a physical barrier at a precise point which halts furtherrotational and vertical motion of the positioning member 140.

In some embodiments, the locking mechanism 160 can be a feature of thesample container 100 that is separate and distinct from the positioningmember 140. In some embodiments, the locking mechanism 160 can be alocking pin or bolt. In some embodiments, the locking mechanism 160 canbe a strap. In some embodiments, the locking mechanism 160 can be alatch. In some embodiments, the locking mechanism 160 can bespring-loaded detents that are disposed within a depression once thepositioning member 140 is appropriately positioned on a surface of theimaging device or within the aperture in a surface of the imagingdevice. In some embodiments, the locking mechanism 160 can include anycombination of the features and elements included herein.

In some embodiments, the locking mechanism 160 can be made frompolyvinyl chloride, polypropylene, polyethylene, polystyrene, nylon,polyethylene terephthalate, polyimide, polycarbonate, acrylonitrilebutadiene, polyetheretherketone, polyurethane, steel, stainless steel,aluminum, copper, lead, zinc, silver, titanium, tin chromium, platinum,molybdenum, magnesium, cobalt, tungsten, manganese, mercury, cadmium,niobium, circonium, vanadium, tantalum, palladium, rhodium, beryllium,indium, thorium, iridium, lithium, lanthanum, barium, rhenium, carbonfiber, and any combinations or admixtures thereof.

FIGS. 2-4 illustrate a sample container 200 according to an embodiment.As described above with reference to the sample container 100, thesample container 200 (also referred to herein as “specimen container” or“sample holder”) is configured to hold an excised biological sample in afixed position or a substantially fixed position so that examinationand/or analysis can be performed after excision. In some embodiments,portions and/or aspects of the sample container 200 are substantiallysimilar in form and/or function to the corresponding portions and/oraspects of the sample container 100 described above with reference toFIG. 1. Accordingly, such similar portions and/or aspects are notdescribed in further detail herein.

As shown in FIG. 2, the sample container 200 includes a sample bag 210defining an inner volume configured to receive a biological tissuesample, and a sealing member 220 coupled to the sample bag 210. Apositioning member 240 is disposed against the sealing member 220 andsubstantially seals the inner volume. Referring now also to FIG. 3, animaging window 230 is coupled to the positioning member 240 and isdisposed and configured to be placed in contact with at least a portionof the biological sample. As described herein, the positioning member240 can be coupled to and/or integrally formed with the imaging window230. In some embodiments, the positioning member 240 can benon-uniformly shaped and the sealing member 220 can be dimensioned andconfigured such that the abutment of the sealing member 220 against thepositioning member 240 can result in the sample container 200 beingsubstantially sealed.

In some embodiments, the positioning member 240 defines the aperture 242approximately in the center of the positioning member 240, and theimaging window 230 is disposed within the aperture 242. In someembodiments, the imaging window 230 is coupled to the positioning member240 such that a substantially airtight seal is formed. In someembodiments, the positioning member 240, the imaging window 230, thesealing member 220, and the sample bag 210 collectively define the innervolume within which the biological sample is disposed during analysis.

As described herein, the positioning member 240 can be dimensioned andconfigured to abut a portion of an imaging device (not shown) toposition the sample of biological tissue in three-dimensional spacerelative to a lens or probe of the imaging device. For example, as shownin FIGS. 3 and 4, the locking mechanism 260 includes a first channel 264configured to retain the positioning member 240 in place. In someembodiments, the first channel 264 has a first end 265 a and a secondend 265 b, the first end 265 a being open and the second end 265 b beingsubstantially closed defining a first stop. In some embodiments, thefirst channel 264 is dimensioned and configured such that thepositioning member 240 rotatably and lockably engages the imagingdevice.

In other words, in some embodiments the positioning member 240 can beconnected to a receiving section of the imaging device in order for aridge (not shown) or a thread (not shown) to fit into the channel 264.The positioning member 240 can then be rotated until either a) alignmentmarkings are in alignment, b) until rotation is stopped by the ridge orthread coming to rest against the stop, c) a magnetic sensor senses thepresence of the positioning member 240 and alignment thereof with regardto the receiving section of the imaging device, d) until the vacuumports 250 are aligned with the vacuum system such that the vacuum systemcan draw air through the vacuum ports 250, or until some other approachterminates rotation or prompts a user (not shown) to stop rotating thepositioning member 240. The user can then place the sealing member 220onto the positioning member 240 and the biological tissue sample canthen be positioned against the imaging window 230.

In some embodiments, a continuous vacuum system is configured such thatthe vacuum system automatically draws air from the sample container 200once the first vacuum port 250 a and/or second vacuum port 250 b and anyadditional vacuum ports, collectively “vacuum ports 250” are alignedwith the corresponding vacuum system ports on the imaging device. Insome embodiments, the continuous vacuum system is a general vacuumsystem in the operating room or other clinical environment and is not apart of the imaging and/or analysis device. In some embodiments, avacuum system remains off until such a time as the sample container 200is in place for analysis and then initiates a vacuum pump or othervacuum device to withdraw air from the sample container 200. In someembodiments, the sample container 200 further includes a magneticalignment device (not shown) that can detect when the vacuum ports 250are aligned with the vacuum system ports. In some embodiments, themagnetic alignment device can alert the user when alignment is achieved.In some embodiments, the magnetic alignment device can be incommunication with a processor and/or with the vacuum system such thatwhen alignment between the vacuum ports 250 and vacuum system ports isachieved the vacuum system automatically begins pumping air from withinthe sample container 200. Once the vacuum system is initiated, air canbe withdrawn from within the sample bag 210, the sample bag 210 beingdrawn down against the biological tissue sample, holding the biologicaltissue sample in a substantially fixed position.

FIGS. 5 and 6 illustrate a sample container 300 according to anembodiment. As described above with reference to the sample container100 and the sample container 200, the sample container 300 (alsoreferred to herein as “specimen container” or “sample holder”) isconfigured to hold an excised biological sample in a fixed position or asubstantially fixed position so that examination and/or analysis can beperformed after excision. In some embodiments, portions and/or aspectsof the sample container 300 are substantially similar in form and/orfunction to the corresponding portions and/or aspects of the samplecontainer 100 and or the sample container 200 described above withreference to FIGS. 1-4. Accordingly, such similar portions and/oraspects are not described in further detail herein.

The sample container 300 includes a sealing member 320, an imagingwindow 330, a positioning member 340, and a sample bag (not shown tomore clearly convey the connection between the sealing member 320, thepositioning member 340, and the imaging device). In some embodiments,the sample container 300 can be configured to be connected to theimaging device. In some embodiments, the imaging device includes areceiving member 372 dimensioned and configured to receive at least aportion of the sample container 300. In some embodiments, the receivingmember 372 includes a channel 364 configured to receive a portion of thepositioning member 340 in order to aid a user (not shown) in locking thepositioning member 340 to the imaging device. In some embodiments, thereceiving member 372 can include stops 374 that are dimensioned andconfigured to terminate rotation of the positioning member 340. In someembodiments, the stops 374 can be magnetized and/or electricallyconnected to an alignment monitoring system (not shown) which notifiesthe user when the stops 374 are contacted. In some embodiments, thealignment monitoring system is in communication with the vacuum systemsuch that, once alignment is confirmed by the alignment monitoringsystem, the vacuum system is initiated and air is withdrawn from thesample bag, drawing the sample bag around a biological tissue sample(not shown).

In some embodiments, the positioning member 340 can include an alignmentfeature 368 that provides the user with a visual indication of alignmentof the positioning member 340 with regard to the imaging device. In someembodiments, the alignment feature 368 is a tab that protrudes radiallyoutward from the center of the positioning member 340 which indicatesalignment of a vacuum port 350 with the vacuum system port 366.

In some embodiments, the sample container 300 can further include alocking mechanism 360 that holds the positioning member 340 in properposition, as shown in FIG. 6. Proper alignment of the positioning member340 with respect to the imaging device can result in the vacuum port 350being properly aligned above the vacuum system port 366, with verylittle or no clearance between the two ports. In some embodiments, therotation of the positioning member 340 causes the engagement of thelocking mechanism 360. In some embodiments, engaging the lockingmechanism 360 moves the positioning member 340 closer towards thereceiving member 372, causing the vertical gap between the vacuum port350 and the vacuum system port 366 to close. This can help form a tightseal between the vacuum port 350 and vacuum system port 366 such thatthe vacuum system can better withdraw air from the sample bag.

Any of the sample containers 100, 200, 300, or 400 described herein(collectively “sample container”) may be used to contain a biologicaltissue sample 402 during imaging and/or analysis. The sample container400 may be used to provide a systematic means of communicating tissuesample orientation information relative to a reference point, such as ona patient's body for example, by using certain markers such as, but notlimited to, radio opaque tags and imaging marking beads, for example.The sample container 400 may also be used to prevent sample mix-up andenforce a single-usage policy through the use of mechanical tabs and/orRFID tags, for example. The sample container 400, or a variant thereof,may also include a peel-off mechanism to expose a sterile portion of thesample container 400 that interfaces with a tissue handling system ofthe imaging system. For example, a portion of the sample container 400may be initially covered by a material so that there is no directcontact between the operator and that portion of the sample container400 during the loading and assembly of the sample container 400. Theprotected portion may then be exposed by peeling the protective materialoff of the sample container 400 prior to loading the container onto orinto the imaging system. This may prevent blood or other fluids on theoperator's gloves from being transferred into the scanning region of theimaging system. Furthermore, the sample container 400, or a variantembodiment thereof, may provide a means of trimming a guide wire priorto scanning. This may be realized by a detachable wire cutter mechanismresembling a nail trimmer that is packaged as an integral part of thesample container 400.

The sample container 400, and variants thereof, may provide safe andconsistent handling of a tissue sample when attempting to image itsentire surface. For example, the sample container 400 permits safeinversion of a contained tissue sample so that opposing surfaces can beimaged (or scanned). As another example, the sample container 400 mayinclude orientation cues (or fiducials) that may permit consistenthandling of the contained tissue sample by preserving the orientation ofthe contained tissue sample. In some embodiments, the contained tissuesample may be uniquely associated with particular patient informationthrough the use of bar-codes and/or RFID tags applied to the samplecontainer 400. This may provide a unique association between the patientinformation and the tissue sample that may reduce the mix-up of patientsamples. In some example embodiments, the RFID tag or mechanical tabscan be further used to enforce single use of the sample container 400 sothat the potential for cross-contamination of tissue samples isminimized. Finally, the sample container 400 may include an integratedtrimmer tool that may be used to cut the guide wire, which is typicallyplaced in a suspect region of the tissue sample as a pre-operativeprocedure, prior to imaging the tissue sample.

For example, one potential use scenario of the sample container 400could involve placement of the biological tissue sample 402 in thesample container 400, scanning of the biological tissue sample 402 usingOCT, transmission of the sample container 400 (still containing thebiological tissue sample) to a radiology or MRI department, scanning ofthe sample container 400 using X-RAY or MRI while the biological tissuesample 402 is still in the sample container 400, and then the submergingof the biological tissue sample 402 in a preserving fluid such asformalin to preserve the biological tissue for longer-term storage. Insome embodiments, the sample container 400 can be sealable, so thesample container 400 may allow the biological tissue sample 402 to beheld in place within formalin until the biological tissue sample 402 islater imaged, stored or otherwise processed.

It should be noted that once the biological tissue sample 402 in thesample container 400 is scanned using another modality, in addition toOCT for example, the imaging data from the other modality could beco-registered with the OCT image data. In other words, one of thepotential benefits of the sample containers disclosed herein, e.g., 100,200, 300, and 400, is that is the comparability of imaging and analysisvia different imaging devices, at different locations, and/or after anelapsed period of time. This is at least in part because the biologicaltissue sample 402 may be maintained in the same position, orientationand/or under the same compressive force (which can cause beneficialaxial compression of the sample) when undergoing two or more differenttypes of imaging or when imaging after an extended period. In otherwords, because the sample bag 410 and the imaging window 430 firmlyengage the biological tissue sample 402 to keep the biological tissuesample 402 in place, the position and orientation repeatability betweendifferent analysis or imaging events can be maintained. In addition,since the imaging window 430 is sufficiently transparent for thedifferent imaging modalities, the sample container 400 does notinterfere with the various analysis or imaging events and the integrityof the various imaging and analysis results is maintained. In addition,because the orientation markers can be used to aid positioning of thesample container 400 with respect to the imaging device when using thedifferent imaging modalities, the orientation markers being opaque tothese imaging modalities, the sample container 400 can be consistentlypositioned with respect to the imaging device leading to more consistentresults. A user 480 could then view the two images on the sameinterface. For example, if the sample container 400 underwent X-rayimaging after OCT imaging, the user 480 could view the radiographinformation alongside the OCT image data in the same interface and infercharacteristic information about the excised biological tissue sample402 from both imaging results without being required to considerposition, orientation, and/or sample shape changes between imagingmodalities. Alternatively, if the other modality is MRI Imaging, thenhi-resolution data for the surface of the MRI image could be obtained byoverlaying the OCT image data on the MRI image data. It should be notedthat this technique may be used with the other embodiments of the samplecontainer 400 described herein.

For many imaging and/or analysis techniques, the biological tissuesample 402 should be positioned very precisely to facilitate accurateanalysis/imaging. For instance, OCT imaging uses near-infrared light toproduce high-resolution images of various objects such as, but notlimited to tissue, for example. When OCT imaging is used on tissue, itis analogous to high-frequency ultrasound, except that the opticalinterferometry of OCT imaging is used for depth ranging rather than echotiming. OCT imaging is rapid, non-contact, non-invasive, and capable ofgenerating 2D and 3D images at high resolution (˜10 μm). In OCT imaging,the registration of the imaging window 430 can be important because theOCT image has micron level resolution and a shallow depth of field. Thismeans the imaging window 430 should be positioned with a high level ofaccuracy relative to the imaging plane. Therefore, in some embodiments,the sample container 400 and/or the imaging device can include spacersand/or raised surfaces that result in the imaging window 430 beingplaced into a precise position once a positioning member 440 is disposedto the imaging device.

In addition, for many of the imaging and/or analysis techniquestypically used to examine the excised biological tissue sample 402, thebiological tissue sample 402 should remain substantially motionlessduring the analysis/imaging period. After excitation of the biologicaltissue sample 402, especially if the tissue sample is not cleaned and/ordried before analysis, can be quite slippery and therefore difficult tohandle during imaging and/or analysis. A practitioner holding thebiological tissue sample 402 can often find it difficult to keep thesample in a particular location during imaging and/or analysis. The useof compression plates to hold the excised biological tissue sample 402in place for imaging and/or analysis has been tried, however, the flatsurface of the compression plates are typically unable to contain theslippery specimen. Therefore, it can be especially important to have aparticularly contoured surface that contacts and holds the biologicaltissue sample 402 in place during analysis/imaging. A molded contactsurface, however, is molded for a particular excised biological tissuesample 402 and may not be useful for specimens of different size and/orshape. Therefore, using the sample bag 410 as a contacting surface forthe biological tissue sample 402 can increase the ease with which thebiological tissue sample 402 is held substantially motionless duringanalysis/imaging.

In some embodiments, the sample bag 410 can have a first configurationin which the sample bag 410 is fully expanded such that the inner volumeis maximized and a second configuration in which the sample bag 410 isdrawn substantially tightly around the biological tissue sample 402 suchthat the inner volume is minimized. In some embodiments, the biologicaltissue sample 402 can be disposed within the sample container 400immediately after excision of the biological tissue sample 402 from thepatient. In some embodiments, the sample container 400 can be positionedin close proximity to the location where surgical excision of thebiological tissue sample 402 takes place such that the biological tissuesample 402 can be easily and quickly disposed within the samplecontainer 400, the sample container 400 containing the biological tissuesample 402 then being transported to the imaging device for analysis. Insome embodiments, the imaging device can also be positioned in closeproximity to the location where surgical excision of the biologicaltissue sample 402 takes place. In some embodiments, the imaging deviceis in a third location outside of the location where surgical excisionof the biological tissue sample 402 takes place. In other words, thesample container 400 can be used to hold the biological tissue sample402 during analysis, can be used to transport the biological tissuesample 402 from the surgical facility to a separate facility foranalysis, and/or can be used to store the biological tissue sample 402for a period of time.

FIGS. 7A-7E show a method by which a biological tissue sample can bedisposed within a sample container, e.g., the sample container 400.FIGS. 8-13 illustrate a method for holding a biological tissue sample ina substantially fixed position using a sample container, e.g., thesample container 400. While FIGS. 7A-7E illustrate the method using thesample container 400, any of the sample containers described herein(e.g., 100, 200, 300, or the like) could be used according to themethods described herein.

The sample container 400 is configured to hold an excised biologicalsample 402 in a fixed position or a substantially fixed position so thatexamination and/or analysis can be performed after excision. As shown inFIG. 7A, in order to dispose the biological tissue sample 402 within thesample bag 410, the user 480 can invert the sample bag 410 and inserttheir hand through a sealing member 420 into the sample bag 410, thushandling the biological tissue sample 402 with hands covered by theinverted sample bag 410. As shown in FIG. 7B, the user 480 can thendispose the biological tissue sample 402 within the sample bag 410. Asshown in FIG. 7C, the user 480 can then place the biological tissuesample 402 onto an imaging window 430 coupled to the positioning member440. As shown in FIG. 7D, the user 480 can then restore the sample bag410 to its proper, non-inverted configuration and move the sealingmember 420 down around the biological tissue sample 402. As shown inFIG. 7E, the user 480 can then position the sealing member 420 againstthe positioning member 440 to seal the biological tissue sample 402 inthe sample bag 410. In some embodiments, the user 480 can activate avacuum system (not shown) to evacuate air from the sample bag 410,thereby drawing the sample bag 410 into close proximity to thebiological tissue sample 402. As the sample bag 410 is drawn intocontact with the biological tissue sample 402, the sample container 400can be used to maintain the biological tissue sample 402 in a properposition for imaging and/or analysis. In some embodiments, the vacuumsystem used is a general vacuum system within an operating room or otherclinical or surgical environment. In some embodiments, the vacuum systemis automatically activated once alignment of the vacuum ports with thedevice vacuum ports is achieved. In some embodiments, the vacuum systemcan be connected to the sample container 400 before the sample containeris positioned within or upon the imaging device. In other words, thevacuum system can be connected to the sample container, air withdrawnfrom within the sample container, then valves configured to be closed inorder for the sample container to be sealed, and finally the samplecontainer positioned for imaging of the biological tissue sample 402.

FIGS. 8-12 illustrate a method for holding a biological tissue sample ina substantially fixed position using a sample container, e.g., thesample container 400. While FIGS. 8-12 illustrate the method using thesample container 400, any of the sample containers described herein(e.g., 100, 200, 300, or the like) could be used according to themethods described herein.

As shown in FIG. 8, in order to position a biological tissue sample 402precisely for imaging using the sample container 400, a user 480 canfirst move the positioning member 440 into place above a receivingmember 472. In some embodiments, the positioning member 440 can have analignment feature 448. When the positioning member 440 is disposedagainst the receiving member 472, as shown in FIG. 9, the user 480 canposition the sample container 400 such that the alignment feature 448aligns with a first alignment marking 476. Alignment of the alignmentfeature 448 with the first alignment marking 476 indicates to the user480 that the positioning member 440 can be fitted into the receivingmember 472 and rotated to lock the positioning member 440 into place.

As shown in FIG. 10, the user 480 then rotates the positioning member440 until the alignment feature 448 aligns with a second alignmentmarking 478, indicating to the user 480 that a vacuum port (not shown)is properly aligned with a vacuum system port (not shown). In someembodiments, the receiving member 472 includes a stop 474. In someembodiments, the stop 474 is positioned such that when the positioningmember 440 is disposed to the receiving member 472 the stop 474 arrestsvertical, horizontal, and/or rotational motion. In some embodiments, thedimensions and configuration of the stops 474 are such that the imagingwindow 430 is positioned at a precise distance above an imaging/analysisprobe and/or lens and/or discharge point once the rotational and/orvertical motion of the positioning member 440 is arrested by the stop474.

In some embodiments, the positioning member 440 and/or receiving member472 include a magnetic alignment device (not shown) or componentsthereof. In some embodiments, the magnetic alignment device can be asensor attached on the receiving member 472 that is connected to aprocessor, the sensor configured to detect the presence of a magnet at acorresponding location on the positioning member 440, indicatingalignment of the vacuum port with the vacuum system port. In someembodiments, the magnetic alignment device is connected to a light, asounding device, or another alert system such that an indication ofalignment can be communicated to the user 480 when attaching thepositioning member 440 to the receiving member 472. In some embodiments,the sensor can be connected to a circuit such that when the sensorsenses that the positioning member 440 is aligned within the receivingmember 472, a circuit is closed and electrical current is allowed to besupplied to the light, the sounding device (auditory alarm), or otheralert system. In some embodiments, the magnetic alignment device is alsoconnected to the vacuum system such that when alignment is confirmed bythe magnetic alignment device the vacuum system is initiatedautomatically in response.

Once the positioning member 440 is positioned and/or locked against thereceiving member 472 or directly against the imaging device, the user480 can place the biological tissue sample 402 onto the imaging window430, as shown in FIG. 11. In some embodiments, the user 480 can disposethe biological tissue sample 402 into the sample bag 410 andsubsequently invert the sample bag 410, disposing the biological tissuesample 402 onto the imaging window 430, instead of the user 480disposing the biological tissue sample 402 directly onto the imagingwindow 430.

Once the user 480 disposes the biological tissue sample 402 against thesample window 430, the sealing member 420, being coupled to the samplebag 410, can be placed on top of the positioning member 440 such thatthe biological tissue sample 402 is substantially covered by the samplebag 410, as shown in FIG. 12. In some embodiments, the sealing member420 is placed on top of the positioning member 440 and held in place bythe user 480. The user 480 can place one or both hands over the sealingmember 420 and apply pressure against the positioning member 440 for theduration of imaging/analysis. In some embodiments, the sealing member420, to which the sample bag 410 is attached, can be placed on top ofthe positioning member 440 and a seal maintained by the withdrawal ofair from within the sample bag 410 by the vacuum system. In someembodiments, when the vacuum system is not initiated and air is notbeing withdrawn from the sample bag 410, the sample bag 410 maintainsthe first configuration wherein it is generally expanded. In someembodiments, when the vacuum is initiated and air is being withdrawnfrom the sample bag 410, the sample bag 410 transitions to the secondconfiguration wherein it is substantially tightly drawn about thebiological tissue sample 402. In some embodiments, when the sample bag410 maintains the second configuration, the biological tissue sample 402is held substantially immobile and maintains a fixed position or asubstantially fixed position, facilitating more accurate and more rapidimaging and/or analysis by the user 480.

FIG. 13 illustrates a method for holding a biological tissue sample in asubstantially fixed position 10, e.g., during imaging and/or storage.The method 10 includes receiving a biological tissue sample into aninner volume of a sample bag, the sample bag coupled to a sealingmember, at 11. In some embodiments, a user (e.g., a laboratorytechnician, an imaging technician, a nurse, a surgeon, or any otheruser) can dispose the biological tissue sample into the sample bag. Insome embodiments, the user can invert the sample bag, grasp thebiological tissue sample with the inverted bag, and revert the samplebag such that the biological tissue sample remains within the samplebag. In some embodiments, the sample bag can be disposed in anuncompressed, rolled, non-deformed or otherwise flat configuration flushwith a conventional operating room surface or laboratory surface. Forinstance, the sample bag can initially include a receiving tip portionand a rolled sheath portion. In some embodiments, the receiving portionof the sample bag can be configured to receive the biological tissuesample and the rolled sheath portion can be configured to be unrolled tocover the biological tissue sample once the biological tissue sample isdisposed onto the receiving portion of the sample bag.

The method 10 includes disposing an imaging window into contact with aportion of the biological tissue sample, at 12. In some embodiments, theimaging window can be coupled to the sealing member such that theimaging window substantially spans the opening of the sample bag,sealing the biological tissue sample within the inner volume defined bythe sample bag and the imaging window. In some embodiments, the imagingwindow can be slidably disposed within a portion of the sealing member.In some embodiments, the imaging window can be rotatably disposed withinthe sealing member, for instance around a point along an edge orcircumference of the imaging window.

The method 10 optionally includes coupling a positioning member to theimaging window to form a sample container such that the biologicaltissue sample is substantially sealed within the sample container, at13. In some embodiments, the positioning member can include the imagingwindow such that the method does require the positioning member to becoupled to the imaging window. In some embodiments, the imaging windowcan be fused, clamped, soldered, glued, adhered, taped, screwed, nailed,stapled, or coupled to the positioning member. In some embodiments, theimaging window can be coupled to the positioning member such that oncethe sample container is fully assembled, no or substantially no airleaks occur between the positioning member and the imaging window. Insome embodiments, the positioning member can include a centered apertureand a surround. In some embodiments, the surround can include a lip onwhich at least a portion of the imaging window is disposed such that theimaging window spans or substantially spans the centered aperture. Insome embodiments, the lip can include a deformable sealing member ontowhich the portion of the imaging window can be disposed such that anairtight or substantially airtight seal is formed between the deformablesealing member and the imaging window. In some embodiments, the lip canbe positioned on a bottom side of the surround such that the imagingwindow can be disposed between the positioning member and a receivingmember of an imaging device. In some embodiments, the lip can bepositioned on a top side of the surround such that the imaging windowcan be disposed between the positioning member and the sealing member.In some embodiments, the positioning member can include two parts, e.g.,two halves, configured to fit together to form the positioning member.In some embodiments, the lip can be positioned on an inside of one ofthe two parts of the positioning member such that the imaging window canbe interposed between the two parts, the two parts can then be coupledtogether to form the positioning member, and the imaging window can spanor substantially span the positioning member.

The method 10 optionally includes interposing the sealing member betweenthe positioning member and a locking mechanism, the locking mechanismincluding a channel configured to lockably engage a portion of thepositioning member, at 14. In some embodiments, the locking mechanismcan be integral to the positing member. In some embodiments, the lockingmechanism can be a separate component configured to be disposed about,over, or nearby the positioning member and to lockably engage aprotrusion of the positioning member, the protrusion dimensioned andconfigured to lockably engage the channel to stop rotational, vertical,and/or horizontal motion of the positioning member. In some embodiments,the protrusion can be a ridge or a plurality of ridges positioned aboutthe surround of the positioning member.

The method 10 includes removably locking the sample container to areceiving member, at 15. In some embodiments, the sample container canbe rotatably locked to the receiving member. In some embodiments, thereceiving member can include a receiving aperture configured anddimensioned to receive the positioning member or a portion thereof. Insome embodiments, the receiving aperture can define a wall or aplurality of walls or a circular channel having an inner surface. Insome embodiments, the wall or plurality of walls or inner surface of thecircular channel can include a channel. In some embodiments, thepositioning member can have a bottom side that includes one or moreprotrusions configured to fit fixedly into the channel within theaperture of the receiving member to retain the sample container in placerelative to the imaging device. In some embodiments, when thepositioning member is rotated into a locking position within theaperture of the receiving member or otherwise positioned fixedly withrespect to the imaging device, a vacuum port or a plurality of vacuumports within the positioning member, the vacuum ports being configuredto pass therethrough into the inner volume of the sample bag, can bealigned or substantially aligned with a vacuum system, e.g., of theimaging device. In some embodiments, when the vacuum ports are alignedwith the vacuum system, a flow path or a plurality of flow paths aredefined between the vacuum system and the inner volume of the samplebag.

The method 10 includes withdrawing air from the inner volume of thesample bag, at 16. In some embodiments, a portion of the air within thesample bag can be withdrawn. In some embodiments, all or substantiallyall of the air within the sample bag can be withdrawn. In someembodiments, by removing air from within the sample bag, the samplecontainer being airtight or substantially airtight, the sample bag canbe drawn closer about the biological tissue sample. In some embodiments,the vacuum system can be a continuous vacuum system configured such thatthe vacuum system automatically draws air from the sample container oncethe vacuum port or plurality of vacuum ports are aligned with thecorresponding vacuum system ports on the imaging device. In someembodiments, the continuous vacuum system is a general vacuum system inthe operating room or other clinical environment and is not a part ofthe imaging and/or analysis device. In some embodiments, a vacuum systemremains off until such a time as the sample container is in place foranalysis and then initiates a vacuum pump or other vacuum device towithdraw air from the sample container. In some embodiments, the samplecontainer further includes a magnetic alignment device (not shown) thatcan detect when the vacuum ports are aligned with the vacuum systemports. In some embodiments, the magnetic alignment device can alert theuser when alignment is achieved. In some embodiments, the magneticalignment device can be in communication with a processor and/or withthe vacuum system such that when alignment between the vacuum ports andvacuum system ports is achieved the vacuum system automatically beginspumping air from within the sample container. Once the vacuum system isinitiated, air can be withdrawn from within the sample bag, the samplebag being drawn down against the biological tissue sample, holding thebiological tissue sample in a substantially fixed position. In someembodiments, the sample bag can apply some compressive force to thebiological tissue sample such that the biological tissue sample can bedeformed in a controlled and non-destructive manner. In someembodiments, deformation of the biological tissue sample can include alateral deformation of the biological tissue sample such that thebiological tissue sample is lies flatter on the imaging window and sothat more of the biological tissue sample can be sampled in a singlepositioning of the biological tissue sample. In some embodiments, forexample in order to conduct margin analysis of an excised tumor or otherpotentially malignant biological tissue sample, the vacuum system can bedisengaged after initial imaging of the sample. In some embodiments,once the vacuum system is disengaged, the sample bag can be loosenedfrom about the biological tissue sample and the biological tissue samplecan be repositioned (e.g., flipped over a horizontal axis), the vacuumsystem can be re-engaged to drawn the sample bag about the repositionedbiological tissue sample, and secondary imaging can be conducted. Insome embodiments, however, by drawing the sample bag about thebiological tissue sample such that the sample bag applied at least somecompressive force and so that the biological tissue sample is at leastpartially deformed, less repositioning of the biological tissue samplemay be necessary.

To provide an overall understanding, certain illustrative embodimentshave been described; however, it will be understood by one of ordinaryskill in the art that the systems, apparatuses, and methods describedherein can be adapted and modified to provide systems, apparatuses, andmethods for other suitable applications and that other additions andmodifications can be made without departing from the scope of thesystems, apparatuses, and methods described herein.

Unless otherwise specified, the illustrated embodiments can beunderstood as providing exemplary features of varying detail of certainembodiments, and therefore, unless otherwise specified, features,components, modules, and/or aspects of the illustrations can beotherwise combined, separated, interchanged, and/or rearranged withoutdeparting from the disclosed systems or methods. Additionally, theshapes and sizes of components are also exemplary and unless otherwisespecified, can be altered without affecting the scope of the disclosedand exemplary systems, apparatuses, or methods of the presentdisclosure.

The embodiments have been particularly shown and described, but it willbe understood that various changes in form and details may be made.

Conventional terms in the field of medical devices have been usedherein. The terms are known in the art and are provided only as anon-limiting example for convenience purposes. Accordingly, theinterpretation of the corresponding terms in the claims, unless statedotherwise, is not limited to any particular definition. Thus, the termsused in the claims should be given their broadest reasonableinterpretation.

Although specific embodiments have been illustrated and describedherein, it will be appreciated by those of ordinary skill in the artthat any arrangement that is adapted to achieve the same purpose may besubstituted for the specific embodiments shown. Many adaptations will beapparent to those of ordinary skill in the art. Accordingly, thisapplication is intended to cover any adaptations or variations.

The above detailed description includes references to the accompanyingdrawings, which form a part of the detailed description. The drawingsshow, by way of illustration, specific embodiments that may bepracticed. These embodiments are also referred to herein as “examples.”Such examples may include elements in addition to those shown ordescribed. However, the present inventors also contemplate examples inwhich only those elements shown or described are provided. Moreover, thepresent inventors also contemplate examples using any combination orpermutation of those elements shown or described (or one or more aspectsthereof), either with respect to a particular example (or one or moreaspects thereof), or with respect to other examples (or one or moreaspects thereof) shown or described herein.

All publications, patents, and patent documents referred to in thisdocument are incorporated by reference herein in their entirety, asthough individually incorporated by reference. In the event ofinconsistent usages between this document and those documents soincorporated by reference, the usage in the incorporated reference(s)should be considered supplementary to that of this document; forirreconcilable inconsistencies, the usage in this document controls.

In this document, the terms “imaging” or “analysis” are usedinterchangeably here and are not to be considered limiting in any way.In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one, independent of any otherinstances or usages of “at least one” or “one or more.” In thisdocument, the term “or” is used to refer to a nonexclusive or, such that“A or B” includes “A but not B,” “B but not A,” and “A and B,” unlessotherwise indicated. In this document, the terms “including” and “inwhich” are used as the plain-English equivalents of the respective terms“comprising” and “wherein.” Also, in the following claims, the terms“including” and “comprising” are open-ended, that is, a system, device,article, or process that includes elements in addition to those listedafter such a term in a claim are still deemed to fall within the scopeof that claim. Moreover, in the following claims, the terms “first,”“second,” and “third,” etc. are used merely as labels, and are notintended to impose numerical requirements on their objects.

The above description is intended to be illustrative, and notrestrictive. For example, the above-described examples (or one or moreaspects thereof) may be used in combination with each other. Otherembodiments may be used, such as by one of ordinary skill in the artupon reviewing the above description. The Abstract is provided to complywith 37 C.F.R. § 1.72(b), to allow the reader to quickly ascertain thenature of the technical disclosure and is submitted with theunderstanding that it will not be used to interpret or limit the scopeor meaning of the claims.

In this Detailed Description, various features may have been groupedtogether to streamline the disclosure. This should not be interpreted asintending that an unclaimed disclosed feature is essential to any claim.Rather, inventive subject matter may lie in less than all features of aparticular disclosed embodiment. Thus, the following claims are herebyincorporated into the Detailed Description, with each claim standing onits own as a separate embodiment, and it is contemplated that suchembodiments may be combined with each other in various combinations orpermutations. The scope of the embodiments should be determined withreference to the appended claims, along with the full scope ofequivalents to which such claims are entitled.

1.-46. (canceled)
 47. A method for holding a biological tissue sample ina substantially fixed position, the method comprising: receiving thebiological tissue sample into an inner volume of a sample bag, thesample bag coupled to a sealing member; disposing an imaging windowacross an opening of the sample bag such that the imaging window isconfigured to remain in contact with a portion of the biological tissuesample; coupling a positioning member to the imaging window to form asample container such that the biological tissue sample is substantiallysealed within the sample container; removably locking the samplecontainer to a receiving member; and withdrawing air from the innervolume of the sample bag.
 48. The method of claim 47, furthercomprising: interposing the sealing member between the positioningmember and a locking mechanism, the locking mechanism including achannel, the channel having a first end that is substantially open and asecond end that is substantially closed.
 49. The method of claim 47,wherein disposing the imaging window across the opening of the samplebag includes rotatably locking the imaging window to the sealing member.50. The method of claim 48, wherein the locking mechanism includes afirst plurality of vacuum ports and the receiving member includes asecond plurality of vacuum ports, the first plurality of vacuum portsbeing dimensioned and configured to align with the second plurality ofvacuum ports such that a partial vacuum can be formed within the samplecontainer.
 51. The method of claim 49, wherein withdrawing the air fromthe inner volume of the sample bag includes reducing the inner volume ofthe sample bag such that the sample bag maintains the biological tissuesample in substantially the same position against the imaging windowduring analysis.
 52. A method for forming a sample holder configured tohold a biological tissue sample in a substantially fixed position, themethod comprising: coupling a sample bag to a sealing member; disposingan imaging window across an opening of the sample bag such that an innervolume of the sample bag is substantially airtight; coupling the samplebag to a locking mechanism by disposing the sample bag through anaperture of the locking mechanism such that the imaging window isdisposed against a surface of the locking mechanism, the lockingmechanism defining a channel and including a first plurality of vacuumports, the channel including a first end that is open and a second endthat is closed; rotatably coupling the locking mechanism to a receivingmember, the receiving member including a ridge configured to be slidablydisposed within the channel and a second plurality of vacuum ports, thesecond plurality of vacuum ports configured to be substantially alignedwith the first plurality of vacuum ports when the locking mechanism isrotatably coupled to the receiving member. 53.-54. (canceled)
 55. Themethod of claim 47, wherein the sealing member includes at least twoportions coupled together mechanically or with an adhesive, the samplebag coupled to the sealing member by being interposed between the atleast two portions of the sealing member.
 56. The method of claim 47,further comprising: transitioning the sample bag from a non-invertedconfiguration into an inverted configuration; disposing the sample bagin the inverted configuration over the biological tissue sample; andmoving the sealing member down around the biological tissue sample torestore the sample bag to the non-inverted configuration and receive thebiological tissue sample into the inner volume of the sample bag. 57.The method of claim 56, wherein moving the sealing member down aroundthe biological tissue sample includes moving the sealing member to bepositioned against the positioning member.
 58. The method of claim 47,wherein: the sample bag includes a receiving tip portion and a rolledsheath portion prior to receiving the biological tissue sample into theinner volume of the sample bag, and receiving the biological tissuesample into the inner volume of the sample bag includes: disposing thereceiving tip portion of the sample bag over the biological tissuesample; and unrolling the rolled sheath portion of the sample bag tocover the biological tissue sample after the receiving tip portion ofthe sample bag is disposed over the biological tissue sample.
 59. Themethod of claim 47, wherein the receiving member includes a receivingaperture configured to receive at least a portion of the positioningmember when the sample container is removably locked to the receivingmember.
 60. The method of claim 47, further comprising: communicatingelectromagnetic energy from an imaging device, through the imagingwindow, to the biological tissue sample.
 61. The method of claim 47,wherein removably locking the sample containing to the receiving memberincludes: disposing a portion of the positioning member in a channel ofthe receiving member; rotating the positioning member until the portionof the position member comes into contact with a registration pointdisposed about the receiving member.
 62. The method of claim 61, whereinthe registration point is configured to arrest movement of thepositioning member after the portion of the position member is disposedin the channel.
 63. The method of claim 52, wherein the lockingmechanism is coupled to a positioning member, and rotatably locking thelocking mechanism to the receiving member includes: fitting the ridgeinto the channel when an alignment element coupled to the positioningmember is aligned with a first alignment marking indicating the firstend of the channel; and rotating the positioning member until thealignment element aligns with a second alignment marking indicating thesecond end of the channel.
 64. The method of claim 63, wherein alignmentbetween the alignment element and the second alignment marking indicatesalignment of the first plurality of vacuum ports with the secondplurality of vacuum ports.
 65. The method of claim 52, wherein thelocking mechanism is coupled to a positioning member, and rotatablylocking the locking mechanism to the receiving member includes fittingthe ridge into the channel and rotating the positioning member until theridge abuts the second end of the channel.
 66. The method of claim 52,further comprising: detecting, via an electronic sensor, alignment ofthe first plurality of vacuum ports with the second plurality of vacuumports; and in response to detecting the alignment of the first pluralityof vacuum ports with the second plurality of vacuum ports, activating avacuum system to withdraw air from the inner volume of the sample bag.67. The method of claim 66, wherein the electronic sensor is configuredto close a circuit in response to the alignment of the first pluralityof vacuum ports with the second plurality of vacuum ports.
 68. Themethod of claim 67, further comprising at least one of producing anaudible sound with an audible alarm connected to the circuit orilluminating an indicator light connected to the circuit, when thecircuit is closed.